Marc van der Kamp

Postdoctoral Fellow
Department of Bioengineering
University of Washington

Ph.D. School of Chemistry
Centre for Computational Chemistry, Mulholland Group
University of Bristol (United Kingdom)

MSc. Molecular Sciences
Wageningen University (the Netherlands)

mwvdk(at)u.washington.edu

Research | top

Since my early undergraduate years, I've been interested in what makes organisms tick (and move, breathe, get ill, get better etc. etc.), on the atomic level. Whilst doing research projects for my MSc degree, I found that by using computers to study biological macromolecules (in particular proteins), one can obtain insight at an extraordinary high level of resolution. Computer simulations, especially when carefully compared to experiment, can therefore serve as a valuable tool to understand life at the atomic level.
Whilst my PhD research primarily focused on the understanding of enzyme catalysis (using QM/MM methods), my current work focusses on the dynamical behaviour of proteins. One particularly interesting case is the Prion protein. The precise function of this protein is still elusive, but it is mostly known (and named) for its propensity to misfold and cause disease. In fact, intial aggregates of the misfolded protein are toxic - i.e. cause neurodegenerative diseases such as Creutzfeld-Jakob disease - and infectious - the aggregates can move from one host to another, transmitting disease, for example from cow to man. I currently use molecular dynamics simulations to gain insight into the early mechanism of misfolding of the prion protein, and suggest models for aggregates based on these simulations. Low pH is known to destabilize the protein and increase the propensity to misfold, as are a range of mutations that are the cause of inherited prion disease. By simulating the Prion protein under these conditions (low pH, mutations) changes in structure and dynamics are uncovered. Studies to clarify how this is affected by glycosylation and membrane-anchoring are underway.

Publications | top

• Van der Kamp MW and Daggett V. The consequences of pathogenic mutations to the human prion protein. Protein Engineering, Design and Selection, in press, 2009. [DOI]
• Van der Kamp MW and Mulholland AJ. Computational enzymology: insight into biological catalysts from modelling. Natural Products Reports, 25: 1001-14, 2008.
• Van der Kamp MW, Shaw KE, Woods CJ and Mulholland AJ. Biomolecular simulation and modelling: status, progress and prospects. Journal of the Royal Society: Interface, 5 (Suppl 3): S173-90, 2008
• Van der Kamp MW, Perruccio P and Mulholland AJ. High-level QM/MM modelling predicts an arginine as the acid in the condensation reaction catalysed by citrate synthase. Chemical Communications, 2008, 1874-1876.
• Van der Kamp MW, Perruccio P and Mulholland AJ. Substrate polarization in enzyme catalysis: QM/MM analysis of the effect of oxaloacetate polarization on acetyl-CoA enolization in citrate synthase. Proteins: Structure, function and bioinformatics, 69: 521-535, 2008.
• Van der Kamp MW, Perruccio P and Mulholland AJ. Journal of Molecular Graphics and Modelling, 26: 596-601, 2007.
• Rodriquez A, Oliva C, Gonzalez M, Van der Kamp M and Mulholland AJ. Journal of Physical Chemistry B, 111: 12909-12915, 2007.

---

Daggett Group
Department of Bioengineering
University of Washington
Benjamin Hall Interdisciplinary Research Building, Suite 300H
616 NE Northlake Place
Seattle, WA 98105